Journal
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
Volume 53, Issue 8, Pages 1017-1026Publisher
SCIENCE PRESS
DOI: 10.1093/abbs/gmab082
Keywords
miR-139-5p; NPTX1; high fatty acid; insulin secretion; INS-1
Categories
Funding
- National Natural Science Foundation of China [81570734]
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The study showed that high fatty acids reduce insulin secretion in pancreatic beta-cells by increasing miR-139-5p, which in turn targets NPTX1. Knockdown of miR-139-5p reversed the insulin secretion defects induced by high fatty acids, indicating that impaired NPTX1 expression is involved in this process.
High fatty acid reduces insulin secretion in pancreatic beta-cells and miR-139-5p is increased in diabetic pancreatic tissues and induces islet beta-cell apoptosis. However, to date, there is no study exploring whether or not miR-139-5p is involved in high fatty acid-induced insulin secretion. In the present study, INS-1 cells were exposed to different concentrations (0.1, 0.2, and 0.4 mM) of palmitate for different time periods (12, 24, and 48 h). The expression levels of miR-139-5p and neuronal pentraxin 1 (NPTX1) were evaluated by real-time PCR and western blot analysis. The regulation of NPTX1 by miR-139-5p was examined by luciferase assay. Cell transfection was conducted using Lipo8000 or Lipofectamine RNAiMAX. Potassium or glucose-stimulated insulin secretion levels were used to verify the function of miR-139-5p or NPTX1 in insulin secretion. Insulin secretion levels were detected by radioimmunoassay. We found that miR-139-5p was increased in INS-1 cells stimulated with palmitate. In addition, miR-139-5p was also elevated in islets of high-fat diet-fed mice and db/db mice compared to those in islets of normal diet-fed mice and wild-type mice. Knockdown of miR-139-5p could reverse high fatty acid-induced insulin secretion defects in INS-1 cells. Furthermore, we demonstrated that NPTX1 is a target of miR-139-5p. miR-139-5p mediated palmitate-induced insulin secretion defects by targeting NPTX1. Moreover, palmitate treatment declined the expression of NPTX1 and the NPTX1 expression was also decreased in islets of high-fat diet-fed mice and db/db mice. Impaired NPTX1 expression is involved in fatty acid-induced insulin secretion defects. Collectively, our results illustrate that the induction of beta-cell insulin secretion defects by fatty acids is mediated, at least in part, by miR-139-5p via downregulation of NPTX1 expression.
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